Christopher A. Loffredo

Failure to diagnose congenital heart disease in infancy.

Objective. To identify factors that predict failure to diagnose congenital heart disease in newborns. Design. All fatal cases in the Baltimore-Washington Infant Study were compiled. The Baltimore-Washington Infant Study includes 4390 cases of infants with congenital cardiovascular malformations identified in a population-based study between 1981 and 1989 in the Baltimore-Washington metropolitan area. Death occurred in 800 such infants in the first year of life. In 76 of these infants, death occurred before diagnosis of heart disease. These cases were identified by community search of autopsy records. Their characteristics are compared with those of infants who died after a cardiac diagnosis was made. Results. Infant characteristics (birth weight, gestational age, intrauterine growth retardation, and chromosomal anomaly) are associated with death of infants with congenital cardiovascular malformations and with death of such infants before diagnosis. Diagnoses of coarctation of the aorta, Ebsteins anomaly, atrial septal defect, and truncus arteriosus are overrepresented in infants found by community search, particularly in those infants without associated malformations. Paternal education is associated with failure to diagnose congenital heart disease in life but other sociodemographic characteristics of the infants family are not. Conclusions. Diagnosis of congenital cardiovascular malformations requires close observation in the neonatal period. Analysis of age at death of infants with undiagnosed congenital cardiovascular malformation suggests that such infants may be at risk if discharged within the first 2 days of life.

Variability in human metabolism of arsenic.

Estimating the nature and extent of human cancer risks due to arsenic (As) in drinking water is currently of great concern, since millions of persons worldwide are exposed to arsenic, primarily through natural enrichment of drinking water drawn from deep wells. Humans metabolize and eliminate As through oxidative methylation and subsequent urinary excretion. While there is debate as to the role of methylation in activation/detoxification, variations in arsenic metabolism may affect individual risks of toxicity and carcinogenesis. Using data from three populations, from Mexico, China, and Chile, we have analyzed the distribution in urine of total arsenic and arsenic species (inorganic arsenic (InAs), monomethyl arsenic (MMA), and dimethyl arsenic (DMA). Data were analyzed in terms of the concentration of each species and by evaluating MMA:DMA and (MMA+DMA):InAs ratios. In all persons most urinary As was present as DMA. Male:female differences were discernible in both high- and low-exposure groups from all three populations, but the gender differences varied by populations. The data also indicated bimodal distributions in the ratios of DMA to InAs and to MMA. While the gene or genes responsible for arsenic methylation are still unknown, the results of our studies among the ethnic groups in this study are consistent with the presence of functional genetic polymorphisms in arsenic methylation leading to measurable differences in toxicity. This analysis highlights the need for continuing research on the health effects of As in humans using molecular epidemiologic methods.

Preconceptional folate intake and malformations of the cardiac outflow tract

We compared cases with outflow tract defects (N = 126) with controls representative of the same birth cohort (N = 679). Infants with clinically recognized syndromes were excluded. Daily total maternal folate intake of > or =245 microg was inversely related to risk of cardiac outflow tract defects among those with transposition (odds ratio estimates: 0.65, 0.78, and 0.76 with increasing quartile of daily folate intake), but positively related among those with normally related vessels (corresponding odds ratio estimates: 1.18, 1.59, and 1.68). This difference disappeared when maternal intake of supplemental folic acid of > or =400 microg compared with <400 microg was considered, excluding dietary intake [odds ratio (OR) = 1.04; 95% confidence interval (CI) = 0.5-2.2 for infants with transposition, and OR = 0.91; 95% CI = 0.5-1.8 for those without transposition of the great arteries].

Use of prescription and non-prescription drugs in pregnancy

We analyzed use of therapeutic drugs during pregnancy by 2752 mothers of infants without major congenital malformations. During pregnancy, 68% of the women used at least one prescription or non-prescription drug. Drug use in pregnancy was significantly more common for women who were white, older, married, better educated, of higher income and occupational status, receiving private prenatal care and not living in urban areas. Number of maternal illnesses, higher socioeconomic status, white race, multiparity and use of recreational drugs explained 26% of reported drug use. The mean number of drugs reported (1.2) underestimates total drug exposure due to exclusion of some drug categories including multivitamins and illicit drugs. Since the majority of women giving birth to normal infants report use of at least one pharmacologic agent during pregnancy, attribution of adverse outcome to drug use in an individual case is rarely justified.

Temporal trends in prevalence of cardiovascular malformations in Maryland and the District of Columbia, 1981-1988. The Baltimore-Washington Infant Study Group.

We studied the yearly occurrence of isolated cardiovascular malformations in liveborns for the period 1981–1988 in Maryland and the District of Columbia. We used Poisson regression to fit yearly prevalence at birth as a function of time for all cardiovascular malformation case types combined and for three diagnostic subgroups. We give results separately by diagnostic method and race (white/nonwhite), with categories combined when appropriate. Time trends were similar for both races except in pulmonic stenosis diagnosed by echocardiography. The yearly prevalence for all case types, all races, and all diagnostic methods combined increased from 28 to 43 per 10,000 livebirths over the 8 years, due to an increase in the rate among infants diagnosed by echocar-diography. For every diagnostic type by race group studied, there were increases in the prevalence for those diagnosed by echocardiography and decreases (or no change in one group) for those diagnosed by cardiac catheterization and/or surgery. Although there may have been an increase in actual occurrence of cardiovascular malformation over our study period, it is also possible that wider use of a new echocardiography technology resulted in increased detection.

Nondaily, light daily, and moderate-to-heavy cigarette smokers in a rural area of Egypt: A population-based survey

INTRODUCTIONnUnderstanding tobacco use among nondaily and light daily cigarette smokers is needed because they are dissimilar from other smokers and may require specific prevention efforts.nnnMETHODnWe compared three groups of adult male smokers in rural Egypt: light daily and nondaily smokers versus moderate-to-heavy daily smokers. Data were obtained from a household survey in 2003 in six randomly selected villages in the Nile Delta region of Egypt. There were 7,657 adult participants, of whom 48.6% were male and 51.4% were female. Among them, 1,401 males (37.6%) and 5 females (0.1%) were self-identified as current cigarette smokers; further analysis focused on males. We restricted data analysis to those who reported a stable pattern of 3+ years of smoking. There were 42 nondaily smokers. Daily smokers were subdivided into two groups: light daily smokers (who smoked no more than 10 cigarettes/day; n = 223) and moderate-to-heavy daily smokers (who smoked at least 11 cigarettes/day; n = 769).nnnRESULTSnWe found statistically significant differences between these groups on nearly every measure: nondaily smokers tended to be younger and unmarried, but they also had higher levels of education and professional occupations compared with the other smokers. Nondaily and the light daily smokers were more likely than moderate-to-heavy smokers to be planning to quit and to have self-efficacy for quitting, and they were less likely to be smoking in the presence of their wife and children at home.nnnDISCUSSIONnFurther understanding of nondaily and light daily smokers may aid in tailoring specific interventions.

Vitamin A and cardiac outflow tract defects

To assess the relationship between maternal intake of vitamin A and cardiac outflow tract defects, we examined data from a population-based case-control study among liveborn infants born from 1987 through 1989 to mothers residing in the Baltimore-Washington area. Case infants (126) had a nonsyndromic cardiac outflow tract defect. Control infants (679) did not have birth defects and were a stratified random sample of liveborn infants from the same area. The main exposure was average daily maternal intake of retinol and provitamin A carotenoids from foods and supplements during the year before conception. Compared with an average intake of less than 10,000 IU, retinol intake of 10,000 IU or more from supplements was associated with a ninefold increased risk for transposition of the great arteries (odds ratio = 9.2; 95% confidence interval = 4.0–21.2), but not for outflow tract defects with normally related arteries (odds ratio = 0.8; 95% confidence interval = 0.1–6.6). Similar intakes of carotenoids and dietary retinol were not associated with an increased risk for either type of outflow tract defect.

Evaluation of Papanicolaou Stain for Studying Micronuclei in Buccal Cells Under Field Conditions

OBJECTIVEnTo compare Papanicolaou (Pap) and May-Grünwald Giemsa (MGG) stain as 2 techniques for staining for buccal mucosal cells to detect micronuclei (MN) infield studies.nnnSTUDY DESIGNnEighty cytologic smears (2 per individual) were taken from the buccal mucosa of 40 cigarette smokers recruited at a rural village in Egypt. Forty smears were stained with Pap stain and 40 with MGG stain. All were assessed for cellularity and scored for MN.nnnRESULTSnPap stain was faster and easier to process and transport in the field study than was MGG stain. Regarding MGG smears, bacteria and cell debris masked the MN as compared to Pap smears, in which the fixative destroyed the bacteria and made the cell boundaries clearly demarcated. Using Pap stain, MN were seen easily in transparent cytoplasm.nnnCONCLUSIONnPap stain is the preferred method infield studies for scoring and detecting MN in cells of buccal mucosa.